We have conducted a randomized, double blind placebo controlled study of surgery with or without raloxifene for treatment of pain from endometriosis. Women with chronic pelvic pain and no endometriosis treatment for 6 months undergo laparoscopic excision of endometriosis lesions after monitoring pelvic pain for 1 month. Those with biopsy-proven endometriosis are randomized to daily raloxifene (180 mg) or placebo for six months. Return of pain is defined as 2 months of pain severity equal to that at study entry. Women have a second surgery at 2 years, or when pelvic pain returns earlier. In the most recent review by the Data Safety and Monitoring Board (DSMB), the study was stopped early because those treated with raloxifene experienced return of pain significantly sooner than those taking placebo and had 2nd surgery sooner. At that time, 93 of 127 women who had undergone surgery had biopsy positive endometriosis and were randomized. In the next year we will analyze the study outcome results including the effect of raloxifene on menstrual cycle length and adverse events during treatment. It appears that raloxifene taken after complete excision of endometriosis significantly shortened the time to return of pain. [unreadable] As part of this clinical trial, we have explored other aspects of endometriosis. [unreadable] We have postulated that persistence of dysmenorrhea and nonmenstrual pelvic pain at three months after excision of endometriosis might be associated with adenomyosis as defined by a thickened uterine junctional zone on magnetic resonance imaging. Following surgical excision of endometriosis, chronic pelvic pain was significantly more likely to persist with junctional zone thickness >11mm on preoperative MR imaging. This suggests that myometrial junctional zone abnormalities or adenomyosis may contribute to chronic pelvic pain in women with endometriosis. [unreadable] We have evaluated the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), and breast cancer nuclear receptor auxiliary factor (Brx) in eutopic endometrium of normal women and women with endometriosis. While expression of ERalpha and ERbeta was highest in the proliferative phase and was similar in both groups, the spatiotemporal expression of Brx was altered in eutopic endometrium of women with endometriosis suggesting a fundamental alteration in the endometrium of women who have endometriosis. The role of Brx in ectopic implantation of endometrium deserves further study.[unreadable] In comparing surgical and histopathologic findings, we have previously shown that only about 70% of endometriosis lesions seen at surgery are biopsy proven. To better understand which lesion characteristics correlate with positive histology for endometriosis, we are studying the surgical and histopathologic findings in second group of women undergoing surgery for endometriosis and comparing the findings in the second group to those we have previously reported. We also are developing a predictive logistic regression model by using individual and lesion characteristics. These studies might help surgeons choose lesions that would be subsequently shown to contain histologically confirmed endometriosis.